Asymmetric Mbc, active Rac1 and F-actin foci in the fusion-competent myoblasts during myoblast fusion in <i>Drosophila</i>

Haralalka, Shruti; Shelton, Claude; Cartwright, Heather; Katzfey, Erin; Janzen, Evan; Abmayr, Susan M.

doi:10.1242/dev.092379

Cited by 13 publications

(34 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fusion-competent myoblasts migrate to these founder cells and undergo repeated rounds of myoblast fusion events to form multinucleated muscle fibers (Figure 1, A and B). Consistent with published literature (Erickson et al 1997;Balagopalan et al 2006;Haralalka et al 2011), mutations in mbc resulted in myoblasts that were capable of migrating to the founder cells, but failed to undergo fusion ( Figure 1C, arrowhead).…”

Section: Mbc and Spg Do Not Function Redundantly In Somatic Muscle Desupporting

confidence: 90%

“…Previous experiments to rescue mbc-mediated myoblast fusion defects with the constitutively active form of Rac (Rac1 V12 ) have been difficult to interpret due to the drastic phenotypes of activated Rac on its own ( Figure 2E) and possibly additional functions of Mbc that cannot solely be rescued by a single downstream molecule (Haralalka et al 2011). Thus, we chose a different genetic approach to examine if the Mbc-Elmo complex acts upstream of Rac in myoblast fusion, taking advantage of the GAL4/UAS system (Brand and Perrimon 1993) to drive gene expression in the muscle under control of the mef2 promoter.…”

Section: Mbc and Spg Do Not Function Redundantly In Somatic Muscle Dementioning

confidence: 99%

“…We previously showed that Spg is also expressed in developing neural tissue and essential for axon outgrowth and midline crossing (Biersmith et al 2011). In contrast, Mbc is well characterized for its role in myoblast fusion (Erickson et al 1997;Balagopalan et al 2006;Haralalka et al 2011). At stage 13 in embryogenesis, specialized muscle cells termed "founder cells" are present at sites where somatic muscles will eventually form.…”

Section: Mbc and Spg Do Not Function Redundantly In Somatic Muscle Dementioning

confidence: 99%

See 2 more Smart Citations

Fine-Tuning of the Actin Cytoskeleton and Cell Adhesion During Drosophila Development by the Unconventional Guanine Nucleotide Exchange Factors Myoblast City and Sponge

2015

View full text Add to dashboard Cite

The evolutionarily conserved Dock proteins function as unconventional guanine nucleotide exchange factors (GEFs). Upon binding to engulfment and cell motility (ELMO) proteins, Dock-ELMO complexes activate the Rho family of small GTPases to mediate a diverse array of biological processes, including cell motility, apoptotic cell clearance, and axon guidance. Overlapping expression patterns and functional redundancy among the 11 vertebrate Dock family members, which are subdivided into four families (Dock A, B, C, and D), complicate genetic analysis. In both vertebrate and invertebrate systems, the actin dynamics regulator, Rac, is the target GTPase of the Dock-A subfamily. However, it remains unclear whether Rac or Rap1 are the in vivo downstream GTPases of the Dock-B subfamily. Drosophila melanogaster is an excellent genetic model organism for understanding Dock protein function as its genome encodes one ortholog per subfamily: Myoblast city (Mbc; Dock A) and Sponge (Spg; Dock B). Here we show that the roles of Spg and Mbc are not redundant in the Drosophila somatic muscle or the dorsal vessel. Moreover, we confirm the in vivo role of Mbc upstream of Rac and provide evidence that Spg functions in concert with Rap1, possibly to regulate aspects of cell adhesion. Together these data show that Mbc and Spg can have different downstream GTPase targets. Our findings predict that the ability to regulate downstream GTPases is dependent on cellular context and allows for the fine-tuning of actin cytoskeletal or cell adhesion events in biological processes that undergo cell morphogenesis.

show abstract

Section: Mbc and Spg Do Not Function Redundantly In Somatic Muscle Desupporting

confidence: 90%

Section: Mbc and Spg Do Not Function Redundantly In Somatic Muscle Dementioning

confidence: 99%

Section: Mbc and Spg Do Not Function Redundantly In Somatic Muscle Dementioning

confidence: 99%

See 1 more Smart Citation

Fine-Tuning of the Actin Cytoskeleton and Cell Adhesion During Drosophila Development by the Unconventional Guanine Nucleotide Exchange Factors Myoblast City and Sponge

2015

View full text Add to dashboard Cite

show abstract

“…N-WASp Is Required in both Fusing Partners. A recurrent issue in studies of both Drosophila and mammalian myoblast fusion, with broad mechanistic implications, is whether fusion-related elements function in one or both fusing myogenic cells (19)(20)(21)(22)(23). We therefore used the N-WASp fl/fl -derived satellite-cell cultures to assess the requirement for N-WASp in this context.…”

Section: Conditional Disruption Of Murine N-wasp Results In Abnormal mentioning

confidence: 99%

The actin regulator N-WASp is required for muscle-cell fusion in mice

Gruenbaum-Cohen

Harel²,

Umansky³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A fundamental aspect of skeletal myogenesis involves extensive rounds of cell fusion, in which individual myoblasts are incorporated into growing muscle fibers. Here we demonstrate that N-WASp, a ubiquitous nucleation-promoting factor of branched microfilament arrays, is an essential contributor to skeletal muscle-cell fusion in developing mouse embryos. Analysis both in vivo and in primary satellite-cell cultures, shows that disruption of N-WASp function does not interfere with the program of skeletal myogenic differentiation, and does not affect myoblast motility, morphogenesis and attachment capacity. N-WASp-deficient myoblasts, however, fail to fuse. Furthermore, our analysis suggests that myoblast fusion requires N-WASp activity in both partners of a fusing myoblast pair. These findings reveal a specific role for N-WASp during mammalian myogenesis. WASp-family elements appear therefore to act as universal mediators of the myogenic cell-cell fusion mechanism underlying formation of functional muscle fibers, in both vertebrate and invertebrate species.actin nucleation | myotube formation

show abstract

“…The signaling intermediates include scaffold proteins (ELMO, Blown Fuse, Antisocial) (8)(9)(10), kinase (p21-activated kinase) (11), guanine nucleotide exchange factors (GEFs) [Myoblast City (MBC), Loner] (12, 13), GTPase (Rac), (14) and actin nucleation regulators (Kette, WAVE, WASP, WASP-interacting protein) (15)(16)(17)(18)(19). Some of these proteins ultimately promote the formation of actin-driven podosome-like structures in the fusion-competent cells that invade founder cells for membrane fusion (20,21).…”

mentioning

confidence: 99%

G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates

Hamoud

Tran

Croteau

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

101

113

View full text Add to dashboard Cite

Muscle fibers form as a result of myoblast fusion, yet the cell surface receptors regulating this process are unknown in vertebrates. In Drosophila, myoblast fusion involves the activation of the Rac pathway by the guanine nucleotide exchange factor Myoblast City and its scaffolding protein ELMO, downstream of cellsurface cell-adhesion receptors. We previously showed that the mammalian ortholog of Myoblast City, DOCK1, functions in an evolutionarily conserved manner to promote myoblast fusion in mice. In search for regulators of myoblast fusion, we identified the G-protein coupled receptor brain-specific angiogenesis inhibitor (BAI3) as a cell surface protein that interacts with ELMO. In cultured cells, BAI3 or ELMO1/2 loss of function severely impaired myoblast fusion without affecting differentiation and cannot be rescued by reexpression of BAI3 mutants deficient in ELMO binding. The related BAI protein family member, BAI1, is functionally distinct from BAI3, because it cannot rescue the myoblast fusion defects caused by the loss of BAI3 function. Finally, embryonic muscle precursor expression of a BAI3 mutant unable to bind ELMO was sufficient to block myoblast fusion in vivo. Collectively, our findings provide a role for BAI3 in the relay of extracellular fusion signals to their intracellular effectors, identifying it as an essential transmembrane protein for embryonic vertebrate myoblast fusion. myotube formation | myogenesis | model system | ced-12 | RhoGTP

show abstract

Asymmetric Mbc, active Rac1 and F-actin foci in the fusion-competent myoblasts during myoblast fusion in Drosophila

Cited by 13 publications

References 1 publication

Fine-Tuning of the Actin Cytoskeleton and Cell Adhesion During Drosophila Development by the Unconventional Guanine Nucleotide Exchange Factors Myoblast City and Sponge

Fine-Tuning of the Actin Cytoskeleton and Cell Adhesion During Drosophila Development by the Unconventional Guanine Nucleotide Exchange Factors Myoblast City and Sponge

The actin regulator N-WASp is required for muscle-cell fusion in mice

G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates

Contact Info

Product

Resources

About